A major obstacle in cancer chemotherapy is the emergence of resistance to cytotoxic drugs in tumor cells during treatment. Two central problems are still open: 1) the understanding at molecular level of the mechanism by which cells develop resistance; 2) the acquisition of a simple and rapid method for the diagnosis of resistance in cancer chemotherapy.
The resistant phenotype is characterized by a loss of sensitivity not always against a single drug, but towards a number of chemically unrelated molecules, a behavior known as "Multidrug resistance" (MDR) (1,2).
This complex mechanism is characterized by a reduced intracellular accumulation of the drug resulting from an increased efflux across the plasma membrane (3-5) or from an energy-dependent permeability barrier, which controls the drug entry.(6-9). These mechanisms involve a change in the cell phenotype, which appears at the plasma membrane level. Indeed an altered plasmalemmal composition characterizes MDR cells, with changes in the surface glycoproteins and overexpression of a P-glycoprotein, of molecular weight=170-180kD(8,10).
Several changes in the cell molecular architecture have been recognized (1); however plasma membrane alterations remain the distinctive characteristics of MDR.